Protein marker is tumor specific for clear-cell RCC

Anaheim, CA-Laboratory data from German investigators point to the use of the CD70 protein as a biomarker for clear-cell renal cell carcinoma and suggest that the marker could be useful in differential diagnosis in cases of uncertain histologic classification. This, in turn, could be very important clinically if found to be present in serum or urine.

Among 68 renal tumor samples analyzed, high expression of CD70 was found in all 41 clear-cell tumors, but none was detected in papillary, chromophobe, or oncocytoma cells, said Kerstin Junker, MD, PhD, chief of laboratory molecular biology, department of urology, Friedrich Schiller University, Jena, Germany.

"Until now, there have been no specific tumor markers available for differential diagnosis of renal cell carcinomas," Dr. Junker said at the American Association for Cancer Research annual meeting here.

Tumor-specific marker CD70 is a type-II transmembrane protein belonging to the TNF family. Expression in normal tissues is restricted to antigen-activated T and B lymphocytes and stromal cells of the thymic medulla. It is also the ligand for the receptor of CD27, but its function in tumors is not understood.

"Clear-cell tumors are the most frequent renal tumors, and this marker is only expressed in clear-cell renal cancer tumors," Dr. Junker said. "This means we have a tumor-specific marker we can use to detect the clear-cell tumors."

Dr. Junker said it is difficult to differentiate renal tumors by histology alone. The researchers are now investigating whether CD70 can be detected in urine or serum.

Sixty-eight tumor samples of different histopathologic subtypes were studied, including 41 clear-cell, 19 papillary, five chromophobe renal cell carcinomas, and three oncocytomas as well as their normal tissue counterparts. Immunochemistry was performed on frozen tissue samples using a monoclonal antibody against CD70.

Dr. Junker added that research on the link between CD70 and cancer was not undertaken previously because CD70's only known function was related to the immune system, and it was not suspected of being connected to tumors.

CD70 potential for treatment In a separate presentation here, researchers from Seattle Genetics, Inc., Bothell, WA, reported on an anti-CD70 antibody drug conjugate that appears to kill renal cell carcinoma cells by two different mechanisms.

The in vitro data suggest that CD70 can be exploited as a novel target for antibody-based chemotherapeutic drug delivery for the treatment of renal cell carcinoma.

The conjugate contains a derivative of the microtubule network-disrupting, anti-mitotic agent auristatin, which is selectively cytotoxic against CD70-expressing renal cell carcinoma lines. Auristatin demonstrates potent antitumor efficacy in xenograft models.

Two versions of the antibody drug conjugate 1F6 were found to be selectively cytotoxic against the CD70-positive renal call carcinoma lines, the researchers reported. Additionally, genetically engineered forms of unconjugated 1F6 had potent antibody-dependent cellular cytotoxicity against CD70-positive renal cell carcinoma lines.

The team said these findings suggest that, with appropriate drug linkage, in vivo therapeutic activity of 1F6 may engage both cytotoxic drug targeting and antibody-dependent cytotoxicity for optimal therapeutic effects.